The stressful life events literature suggests an association between the occurrence of major life changes and the incidence of a variety of illnesses. However, since only a minority of individuals who actually experience stressful events actually become ill subsequently, there has been considerable interest in individual differences that presumably mediate the link between stressful events and illness. This proposal addresses the moderating influence of dispositional optimism, a personality variable that appears to modulate the adverse effects of various stressors on both physical and mental health. In this renewal, sequential groups of 30 medical students (total n = 60) will be followed over a 2 1/2 year period, beginning with their entry into medical school. During the first two years, psychological and immunological data will be collected during the first and final examination periods, as well as one month before each; during the last six months, samples will be collected during the second week of each of two two-month clinical rotations. Comparison samples of 20 donors (total n = 40) who are not experiencing cyclical stressors will provide comparable data on the same days. The proposed studies in this renewal also address possible immunological mechanisms that may underlie changes previously observed in cellular immunity during stressful periods, particularly the production of lymphokines and certain cell functions associated with lymphokine production. Very few studies have simultaneously shown a confluence among psychological distress, altered immunity, and actual health changes. The 2 1/2 year data collection period will help to reliably identify characteristics of those individuals who are at greatest risk for actual health changes. The serial assessment of multiple interdependent immunological parameters focusing on cell-to-cell interactions will provide valuable data on the effects of repeated stressor exposure, the moderating influence of optimism, and excellent information on health risks.